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Diffusion imaging and tractography enable mapping structural connections in the human brain, in-vivo. Linear Fascicle Evaluation (LiFE) is a state-of-the-art approach for pruning spurious connections in the estimated structural connectome, by optimizing its fit to the measured diffusion data. Yet, LiFE imposes heavy demands on computing time, precluding its use in analyses of large connectome databases. Here, we introduce a GPU-based implementation of LiFE that achieves 50-100x speedups over conventional CPU-based implementations for connectome sizes of up to several million fibers. Briefly, the algorithm accelerates generalized matrix multiplications on a compressed tensor through efficient GPU kernels, while ensuring favorable memory access patterns. Leveraging these speedups, we advance LiFE’s algorithm by imposing a regularization constraint on estimated fiber weights during connectome pruning. Our regularized, accelerated, LiFE algorithm (“ReAl-LiFE”) estimates sparser connectomes that also provide more accurate fits to the underlying diffusion signal. We demonstrate the utility of our approach by classifying pathological signatures of structural connectivity in patients with Alzheimer’s Disease (AD). We estimated million fiber whole-brain connectomes, followed by pruning with ReAl-LiFE, for 90 individuals (45 AD patients and 45 healthy controls). Linear classifiers, based on support vector machines, achieved over 80% accuracy in classifying AD patients from healthy controls based on their ReAl-LiFE pruned structural connectomes alone. Moreover, classification based on the ReAl-LiFE pruned connectome outperformed both the unpruned connectome, as well as the LiFE pruned connectome, in terms of accuracy. We propose our GPU-accelerated approach as a widely relevant tool for non-negative least-squares optimization, across many domains.
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This content will become publicly available on February 1, 2026
Network Diffusion-Constrained Variational Generative Models for Investigating the Molecular Dynamics of Brain Connectomes Under Neurodegeneration
Alzheimer’s disease (AD) is a complex and progressive neurodegenerative condition with significant societal impact. Understanding the temporal dynamics of its pathology is essential for advancing therapeutic interventions. Empirical and anatomical evidence indicates that network decoupling occurs as a result of gray matter atrophy. However, the scarcity of longitudinal clinical data presents challenges for computer-based simulations. To address this, a first-principles-based, physics-constrained Bayesian framework is proposed to model time-dependent connectome dynamics during neurodegeneration. This temporal diffusion network framework segments pathological progression into discrete time windows and optimizes connectome distributions for biomarker Bayesian regression, conceptualized as a learning problem. The framework employs a variational autoencoder-like architecture with computational enhancements to stabilize and improve training efficiency. Experimental evaluations demonstrate that the proposed temporal meta-models outperform traditional static diffusion models. The models were evaluated using both synthetic and real-world MRI and PET clinical datasets that measure amyloid beta, tau, and glucose metabolism. The framework successfully distinguishes normative aging from AD pathology. Findings provide novel support for the “decoupling” hypothesis and reveal eigenvalue-based evidence of pathological destabilization in AD. Future optimization of the model, integrated with real-world clinical data, is expected to improve applications in personalized medicine for AD and other neurodegenerative diseases.
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- Award ID(s):
- 1944247
- PAR ID:
- 10615491
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- International Journal of Molecular Sciences
- Volume:
- 26
- Issue:
- 3
- ISSN:
- 1422-0067
- Page Range / eLocation ID:
- 1062
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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